One of the most fundamental limitations to reducing mortality due to a number of diseases, including cancer, is the fact that current medical imaging techniques, such as CT and MRI, provide detailed anatomical snapshots of the body but fail to provide accurate, basic information necessary to manage the patient's disease optimally.
The limitations are manifested in several ways, such as for example in cancer: (1) Small primary tumors go undetected. Even under the best conditions, tumors smaller than 2 mm (roughly 500,000 cells) cannot be seen. (2) Metastatic disease is grossly underdiagnosed, and patients with negative scans for metastases at initial presentation routinely go on to develop, and die, from metastatic cancer. (3) Treatment response to therapy is poorly measured. “Measurable disease” is absent after surgical excision of many tumors. The standard of care is to blindly treat with chemotherapy selected by convention using prior retrospective studies and to consider this treatment a success or failure only in retrospect (e g., failure is when a relapse occurs in less than 5 years). Residual metastatic disease can expand undetected. When metastatic disease leads to a tumor that is large enough to be detected (stage 4), it is often too late for anything but a modest extension in patient lifetime with available treatments.
How can conventional imaging be so far off the mark? One reason is that conventional radiologic approaches produce their images based upon bulk structural and anatomical features of the tissue. For example, the image displayed in MRI is that of protons in water or fat as modified by relative concentration and environment. The degree to which, for example, a tumor can be visualized on conventional CT or MRI is merely a function of the ability of that tumor to differentially scatter, absorb, or emit radiation as compared to the surrounding tissue and inherent background noise. It is not surprising that this signal has little sensitivity and specificity for the detection of a tumor.
The signal can be enhanced, however, through the use of targeted probes. Supramolecular assemblies that can be made to form nanospherical structures for carrying contrast agent, such as liposomes and polymer micelles, offer potential for improving various imaging modalities. Results with such liposomes, however, have essentially been disappointing.
Moreover, equally frustrating is a lack of versatile delivery systems for therapeutics, targeted delivery, and a reliable means of proper dosing and tissue distribution of the therapeutic.